The clinical characteristics of nail involvement in pemphigus patients and the correlation between nail involvement and the severity of pemphigus / 中国医师杂志

Objective:To analyze the clinical characteristics of nail involvement in patients with pemphigus and the correlation between nail damage and the severity of pemphigus.Methods:The clinical data of 23 patients with pemphigus combined with nail damage admitted to the People′s Hospital of Xinjiang Uygur Autonomous Region from January 2011 to August 2019 were retrospectively analyzed, the manifestations of pemphigus combined with nail damage were summarized. The nail damage number of patients with pemphigus complicated with nail damage of different genders were analyzed, as well as the distribution of nail damage in nail and toenail. The titer of anti-desmocoglycoprotein(dsg) antibody was detected in all patients. The relationship between nail damage and disease severity and course in pemphigus patients was analyzed.Results:A total of 132 damage nails were found in 23 patients (14 males and 9 females) with pemphigus, including 66 nails in male, 66 nails in female, 82 nails and 50 toenails. There were 10 forms of nail damage, of which chronic paronychia was the most common. The number of damage nails between different genders in pemphigus patients was statistically significant (χ 2=9.183, P<0.001). The distribution of nail and toenail damage in pemphigus patients was statistically significant (χ 2=10.880, P<0.001). Of the 23 patients, only 3 were positive for dsg1 and 1 was positive for dsg3. There were 19 patients with both positive for dsg1 and dsg3. The titers of dsg1 and dsg3 were compared in 14 patients before and after nail damage. The results showed that the titers of anti-dsg antibody in pemphigus patients after nail damage were significantly higher than before. Thirteen of the 23 patients had nail damage at the time of the initial onset of pemphigus. The nail damage occurred from 6 weeks before the onset to 4 weeks after the onset. The nail damage occurred in 10 patients when the disease recurred. The nail damage occurred within 4 weeks before or at the same time with the blister. Conclusions:The number of damage nails per capita in female patients with pemphigus and nail damage was significantly higher than that in male patients, and nail damage was more common. The titers of anti-dsg antibody will be at a high level when pemphigus patients with nail damage, and the condition gets worse. Nail involvement is positive to the severity of the disease, and it can prolong the time of disease.

Reactivation of PPARα alleviates myocardial lipid accumulation and cardiac dysfunction by improving fatty acid β-oxidation in Dsg2-deficient arrhythmogenic cardiomyopathy

Arrhythmogenic cardiomyopathy (ACM), a fatal heart disease characterized by fibroadipocytic replacement of cardiac myocytes, accounts for 20% of sudden cardiac death and lacks effective treatment. It is often caused by mutations in desmosome proteins, with Desmoglein-2 (DSG2) mutations as a common etiology. However, the mechanism underlying the accumulation of fibrofatty in ACM remains unknown, which impedes the development of curative treatment. Here we investigated the fat accumulation and the underlying mechanism in a mouse model of ACM induced by cardiac-specific knockout of Dsg2 (CS-Dsg2 -/-). Heart failure and cardiac lipid accumulation were observed in CS-Dsg2 -/- mice. We demonstrated that these phenotypes were caused by decline of fatty acid (FA) β-oxidation resulted from impaired mammalian target of rapamycin (mTOR) signaling. Rapamycin worsened while overexpression of mTOR and 4EBP1 rescued the FA β-oxidation pathway in CS-Dsg2 -/- mice. Reactivation of PPARα by fenofibrate or AAV9-Pparα significantly alleviated the lipid accumulation and restored cardiac function. Our results suggest that impaired mTOR-4EBP1-PPARα-dependent FA β-oxidation contributes to myocardial lipid accumulation in ACM and PPARα may be a potential target for curative treatment of ACM.

Autoantibodies against desmoglein 2 are not pathogenic in pemphigus

Abstract Background Anti-desmoglein 1 and 3 autoantibodies justify acantholysis in pemphigus; however, the pathogenesis of anti-desmoglein 2 is hypothetical. Objective To compare the participation of desmogleins 1, 2 and 3 through the production of serum autoantibodies, and protein and gene expression in the skin/mucosa of patients with pemphigus foliaceus and pemphigus vulgaris. Methods The autoantibodies were titrated by ELISA in 202 samples of pemphigus foliaceus, 131 pemphigus vulgaris, 50 and 57 relatives of patients with pemphigus foliaceus and pemphigus vulgaris, respectively, and 114 controls. Protein and gene expressions were determined by immunohistochemistry and qPCR in the skin/mucosa of 3 patients with pemphigus foliaceus and 3 patients with pemphigus vulgaris. Results Higher titers of anti-desmoglein 2 (optical density) resulted in pemphigus foliaceus and pemphigus vulgaris, when compared to controls (0.166; 0.180; 0.102; respectively; p < 0.0001). There was a correlation between anti-desmoglein 2 and anti-desmoglein 1 titers in pemphigus foliaceus (r = 0.1680; p = 0.0206). There was no cross-reaction of anti-desmoglein 2 with desmoglein 1 and 3. Protein overexpression of desmoglein 2 was observed in intact and lesional skin of patients with pemphigus compared to the skin of controls. Internalization granules of desmoglein 1 and 3, but not of desmoglein 2, were observed in lesions of pemphigus foliaceus and pemphigus vulgaris, respectively. Gene overexpression of desmoglein 2 was observed in the mucosa. Study limitations Small sample size for the statistical analysis of protein and gene expression. Conclusion Autoantibodies against desmoglein 2 are not pathogenic in pemphigus; protein and gene overexpression of desmoglein 2 in the skin and mucosa may be involved in acantholysis repair.

Clinical Analysis of Eight Cases of Pemphigus with High Titers of Anti-desmoglein Antibodies in Remission / 中国医学科学院学报

Objective To investigate the clinical manifestations,diagnosis,treatment,and laboratory examination characteristics of 8 pemphigus patients with high titers of anti-desmoglein antibodies in remission. Methods A retrospective study was conducted for the pemphigus patients diagnosed and treated in the department of dermatology from January 2013 to September 2020.The patients should have the serum anti-desmoglein antibodies ≥150 U/ml in remission or the antibody levels dropped less than 20%(calculated based on the maximum detection limit of 150 U/ml)of their initial ones detected before treatment,and the clinical and laboratory data of patients eligible for the inclusion criteria were collected. Results Among the 134 pemphigus patients with available follow-up data during this period,a total of 8 patients met the criteria,with the follow-up period of 21-85 months and the remission duration of 18-70 months.They all received less than or equal to 10 mg/d prednisone and had high titers of anti-desmoglein antibodies.At their first visit,the number of patients with positive anti-desmoglein 1/desmoglein 3 antibodies was 7.Two patients still had high titers of anti-desmoglein 1 antibodies 19 months and 21 months after they achieved remission,and 5 patients had high titers of anti-desmoglein 3 antibodies in 18-70 months.There was one patient showing high titers of both antibodies,especially for anti-desmoglein 1 antibodies.This patient relapsed after 19 months' remission while other patients were still in clinical remission. Conclusions Some pemphigus patients showed persistent high titers of anti-desmoglein antibodies in remission.Anti-desmoglein 3 antibodies were more common to keep positive,while high titer of anti-desmoglein 1 antibodies was less observed.The high titer of anti-desmoglein 1 antibodies had a correlation with recurrence.For the pemphigus patients with long-term clinical remission but high antibody titer,the dosages of corticosteroids should be adjusted carefully according to their actual clinical manifestations and the positive antibody type.For the patients with high titer of anti-desmoglein 1 antibodies,the dosage reduction of corticosteroids should be appropriately slower.

Associations of anti-desmoglein antibodies with clinical phenotypes and disease activity in pemphigus patients and their change patterns / 中华皮肤科杂志

Objective To investigate associations of anti-desmoglein (Dsg1 and Dsg3) antibodies detected by enzyme-linked immunosorbent assay (ELISA) with clinical phenotypes and disease activity in pemphigus patients,and to explore their change patterns.Methods A total of 111 patients with pemphigus were enrolled from Hospital for Skin Diseases,Chinese Academy of Medical Sciences and Peking Union Medical College between January 2015 and January 2018.ELISA was performed to detect serum levels of anti-Dsg1 and anti-Dsg3 antibodies in these patients with different clinical types of pemphigus at different stages,including onset stage,control stage (no new erythema or vesicles occurred in the last 2 or more weeks,and primary lesions began to regress),maintenance stage (the condition had been stable for ≥ 1 month,and treatment was maintained with a low dose of glucocorticoids [prednisone equivalent of ＜ 15 mg/d]),and recurrence stage,and the change patterns of serum levels of anti-Dsg1 and anti-Dsg3 antibodies were analyzed.Statistical analysis was carried out with SPSS 22 software by using oneway analysis of variance for the comparison among groups,and least significant difference (LSD)-t test for multiple comparisons.Results At the disease onset stage,control stage,maintenance stage and recurrence stage,92,53,33,and 9 patients respectively completed the detection.Among the 92 patients with initial onset of pemphigus,the positive rates of anti-Dsg1 and anti-Dsg3 antibodies were 100％ and 2.77％ respectively in 36 patients with pemphigus foliaceus,20％ and 80％ respectively in 10 with mucosaldominant pemphigus vulgaris,and 97.82％,95.65％ respectively in 46 with mucocutaneous pemphigus vulgaris.The serum levels of anti-Dsg1 antibodies in the patients with pemphigus foliaceus significantly differed among the disease onset stage,control stage,maintenance stage and recurrence stage (137.43 ±77.74,13.94 ± 14.81,21.50 ± 58.33,121.13 ± 86.89 U/ml,respectively),the serum levels of anti-Dsg3 antibodies in the patients with mucosal-dominant pemphigus vulgaris also significantly differed among the above clinical stages (125.61 ± 94.81,34.5 ± 16.26,0.6,258 U/ml,respectively),and the serum levels of anti-Dsg1 and anti-Dsg3 antibodies in patients with mucocutaneous pemphigus vulgaris both significantly differed among the above clinical stages(anti-Dsg1 antibody:115.39 ± 70.62,15.74 ± 25.10,3.62 ± 12.09,78.60 ± 92.25 U/ml,respectively;anti-Dsg3 antibody:137.98 ± 81.25,58.14 ± 63.46,29.26 ± 64.70,136.9 ± 101.47 U/ml,respectively).Additionally,the serum levels of anti-Dsg1 antibodies in the patients with pemphigus foliaceus,as well as the serum levels of anti-Dsg3 antibodies in the patients with mucosaldominant pemphigus vulgaris and those with mucocutaneous pemphigus vulgaris,were both significantly lower at the disease control stage and maintenance stage than at the disease onset stage and recurrence stage (all P ＜ 0.05).During the treatment,epitope spreading occurred in 2 patients,and high-titer anti-Dsg antibodies were observed in 4 patients at the stable stage.Conclusion Anti-Dsg antibody spectrum is associated with clinical phenotypes of pemphigus,and its serum levels measured by ELISA can be applied to disease activity monitoring and evaluation of therapeutic efficacy.

Advances in research on the function and disease of desmoglein 2 / 医学研究生学报

Desmoglein (DSG) is an important constituent of desmosome, a single transmembrane glycoprotein that binds to desmocollin (DSC), regulates intercellular adhesion and transmits intracellular and extracelluar signals. Studies have shown that DSG2, one subtype of the DSG, is abnormally expressed in tumor cells and has certain value for targeted treatment and prognosis. This paper reviews the structure, biological functions and related diseases of DSG2 protein.

A study of prevalence of autoantibodies in patients with lichen planus from Mumbai, India

Background: Lichen planus is a common chronically relapsing autoimmune skin condition with poorly understood etiology. Apart from cellular immunity, presence of various antibodies has been hypothesized. Various studies have found the presence of serum anti-nuclear antibody, anti-mitochondrial antibody, anti-desmoglein 1 and 3 antibodies, anti-keratinocyte antibody and anti-thyroglobulin antibody in patients of cutaneous and oral lichen planus. Aim: To study the prevalence of autoantibodies and the clinical spectrum of disease in an Indian patient subpopulation with lichen planus. Methods: A cross-sectional epidemiological study comprising 100 lichen planus patients was conducted in the dermatology outpatient department of Seth G.S Medical College and King Edward Memorial Hospital, Mumbai, Maharashtra, India. Serum concentrations of circulating anti-nuclear antibodies, anti-desmoglein 1 antibody, anti-desmoglein 3 antibody, anti-keratinocyte antibodies, anti-mitochondrial antibodies and anti-thyroglobulin antibodies were determined by indirect immunofluorescence. Pairs of groups were compared using “Student's t-test” for normally distributed continuous data. The “χ2-test” was used for the categorical variables as needed. Statistical significance was set at P < 0.05. Results: It was found that 65 (65%) patients showed the presence of at least one of the six autoantibodies that we studied, while 35 (35%) tested negative for all six of them. Positivity of anti-keratinocyte antibody in 26 (26%), anti-nuclear antibody in 22 (22%), anti-desmoglein 1 antibody in 19 (19%), anti-desmoglein 3 antibody in 16 (16%), anti-mitochondrial antibody in 9 (9%) and anti-thyroglobulin antibody in 6 (6%) patients was detected. It was observed that 55 (71.4%) patients of cutaneous lichen planus, 6 (46.1%) patients of mucosal lichen planus and 4 (40%) patients of cutaneous and mucosal lichen planus overlap showed presence of at least one autoantibody. Conclusion: This study provides the serological parameters of a population of lichen planus from western India. Presence of autoantibodies in lichen planus suggests the possible role of humoral immunity in lichen planus. Identifying antibodies linked to lichen planus may help in identifying suitable diagnostic tests and therapeutic targets. Well-controlled studies with larger sample size are the need of the hour to confirm the role of humoral immunity in lichen planus. Limitations: Studies with a larger number of patients as well as controls should be undertaken to further evaluate the role of autoantibodies in lichen planus.

Fogo selvagem: endemic pemphigus foliaceus

Abstract: Fogo selvagem or endemic pemphigus foliaceus is an autoimmune acantholytic anti-cadherin bullous disease that primarily affects seborrheic areas, which might disseminate. Brazil has the world's largest number of patients, mainly in the Central-West region, but the disease has also been reported in other South American countries. It affects young people and adults who have been exposed to rural areas, with occurrence of familial cases. Anti-desmoglein-1 autoantibodies are directed against desmosomal structures, with loss of adhesion of the upper layers of the epidermis, causing superficial blisters. The etiology is multifactorial and includes genetic, immune, and environmental factors, highlighting hematophagous insect bites; drug-related factors are occasionally involved. Flaccid blisters readily rupture to yield erosive-crusty lesions that sometimes resemble seborrheic dermatitis, actinic keratosis, and chronic cutaneous lupus erythematosus. The clinical presentation varies from localized to disseminated lesions. Clinical suspicion should be confirmed with histopathological and immunofluorescence tests, among others. The progression is usually chronic, and therapy varies according to clinical presentation, but generally requires systemic corticosteroid therapy associated with adjuvant immunosuppressive treatment to decrease the adverse effects of corticosteroids. Once the disease is under control, many patients remain stable on low-dose medication, and a significant proportion achieve remission.

Expression and specific antibody-producing capacity of B lymphocytes infiltrating in lesions of patients with pemphigus vulgaris / 中华皮肤科杂志

Objective To evaluate the specific antibody-producing capacity of locally infiltrating B lymphocytes in lesions of patients with pemphigus vulgaris (PV).Methods Totally,35 patients with PV and 22 healthy controls were enrolled into this study.Skin tissues were resected from blisters or erosions of the patients with PV,and from normal skin of healthy controls.Then,mononuclear cells were isolated from these skin tissues.Flow cytometry was performed to determine the percentages of lymphocytes,CD 19+ B lymphocytes,and desmoglein (Dsg)1-and Dsg3-specific CD19+ B lymphocytes.B lymphocytes isolated from the lesional skin of patients with PV were cultured in vitro.Enzyme-linked immunosorbent assay (ELISA) was conducted to determine titers of anti-Dsg1 and anti-Dsg3 antibodies in the cell culture supernatant.Receiver operating characteristic (ROC) curve analysis was conducted to calculate positive rates of anti-Dsg1 and anti-Dsg3 antibodies.Results The percentages of lymphocytes (17.95％ ± 3.85％) and CD19+ B lymphocytes (4.27％ ± 1.13％) were significantly higher in the lesional skin of PV patients than in the normal skin of healthy controls (7.83％ ± 1.29％,0.61％ ± 0.31％ respectively;t =2.49,U =13.00 respectively,both P ＜ 0.05).Among the CD19+ B lymphocytes in the lesional skin of PV patients,the percentage of CD19qgG+ B cells was (38.33 ± 5.56)％,and percentages of Dsg1-and Dsg3-specific CD19+ B lymphocytes were 12.87％ ± 1.267％ and 10.42％ ± 1.243％ respectively.After the in vitro culture for 6 days,the titers of anti-Dsg1 and anti-Dsg3 antibodies in the cell culture supematant were (4.89 ± 1.56) U/ml and (35.45 ± 13.03) U/ml respectively,with their positive rates being 85％ (17/20)and 95％ (19/20) respectively.Conclusion There are Dsg1-and Dsg3-specific B lymphocytes aggregating in the lesional skin of patients with PV,which can produce anti-Dsg1 and anti-Dsg3 antibodies after in vitro culture.

Pathological features of ectopic lymphoid structure in skin lesions of patients with pemphigus / 中华皮肤科杂志

Objective To investigate pathological features of infiltrating lymphocytes in skin lesions of patients with pemphigus,and to analyze their correlation with titers of anti-desmoglein (Dsg) 1 and anti-Dsg3 antibodies in peripheral blood.Methods A retrospective pathological analysis was performed in 93 patients with pemphigus vulgaris or pemphigus foliaceus,who visited the Department of Dermatology of Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine between 2014 and 2016.For each HE-stained section,the total number of lymphocytes per × 50 microscopic field was counted,and defined as lymphocyte density index.Enzyme-linked immunosorbent assay (ELISA) was conducted to determine the serum titers of anti-Dsg1 and anti-Dsg3 antibodies in the patients with pemphigus.The correlations between the lymphocyte density index and titers of anti-Dsg1 and anti-Dsg3 antibodies were analyzed.Immunohistochemical staining was performed in lesional skin samples from 8 patients with pemphigus vulgaris and 8 patients with pemphigus foliaceus,so as to analyze the distribution of CD3+ T cells,CD20+ B cells and CD138+ plasma cells.Results Of the 93 pathological sections,93 (100.00％) showed Grade1 lymphocyte aggregates,64 (68.09％) showed Grade 2 lymphocyte aggregates,and 10 (10.64％) showed Grade 3 lymphocyte aggregates,and the 56 cases of pemphigus vulgaris and 37 of pemphigus foliaceus showed the similar proportion of grade 1,2 and 3 lymphocyte aggregates.There was also no significant difference in the lymphocyte density index between patients with pemphigus vulgaris and pemphigus foliaceus (P ＞ 0.05),and the lymphocyte density index was uncorrelated with the serum titers of anti-Dsg1 and anti-Dsg3 antibodies in patients with pemphigus.Of the 16 cases of pemphigus,CD3+ T cells were found in all cases,CD20+ B cells in 15,and CD138+ plasma cells in 12.Of 16 sections,all showed a large amount of CD3+ T cells in Grade 1-3 lymphocyte aggregates,while lymphocyte aggregates containing CD20+ B cells and CD138+ plasma cells were found in 52.80％ ± 5.78％ and 34.59％ ± 7.42％ of sections respectively.No significant differences in the distribution of CD3+ T cells,CD20+ B cells,CD138+ plasma cells were found between the 8 cases of pemphigus vulgaris and 8 cases of pemphigus foliaceus.Conclusion Different degrees of lymphocyte infiltration generally exist in skin lesions of patients with pemphigus,which may form ectopic lymphoid structures and contribute to the development and aggravation of pemphigus skin lesions.

Bullous pemphigoid associated with milia, increased serum IgE, autoantibodies against desmogleins, and refractory treatment in a young patient

Abstract: Bullous pemphigoid is a blistering autoimmune disease characterized by two hemidesmosomal proteins (anti-BP180 and 230). Pemphigus, by contrast, is characterized by two autoantibodies (anti-desmoglein 1 and 3). Coexistence of autoantibodies of bullous pemphigoid and pemphigus in a patient is rare. A 25-year-old male patient was admitted to our hospital, reporting a 3-month history of multiple papules, vesicles, and erosions over an extensive erythema on the entire body. Laboratory tests showed high levels of serum IgE, anti-BP180 antibodies, and anti-desmoglein 1 and 3. Histopathologic and immunopathologic features were characterized by bullous pemphigoid. No improvement was seen with systemic corticosteroid therapy, however, pulse corticosteriod therapy combined with methylprednisolone, immunosuppressants, immunomodulators, and plasmapheresis led to the recovery of his condition with numerous milia.

Locations of acantholysis in 71 cases of pemphigus / 中华皮肤科杂志

Objective To analyze locations of acantholysis in pemphigus vulgaris (PV) and pemphigus foliaceus (PF),so as to explain why acantholysis in pemphigus occurs in different locations of the epidermis.Methods Clinical data,histopathological and immunopathological findings,and pemphigus antibody level values were collected from 43 patients with PV and 28 with PF,and retrospectively analyzed.Results Of the 43 patients with PV,35 showed acantholysis in the upper basal layer,8 in the middle-to-upper epidermis.Of the 28 patients with PF,25 showed acantholysis in the granular layer and the upper prickle cell layer,3 in the middle-to-lower epidermis.Patients with PF showed significantly higher levels of anti-Desmoglein 1 (Dsg1) antibody compared with patients with PV (P =0.047).However,there were no significant differences in the levels of anti-Dsg1 and anti-Dsg3 antibodies between PV patients who had acantholysis in the middle-to-upper epidermis and those in the upper basal layer.Conclusion Histopathological examinations of PV and PF lesions show that acantholysis can occur in the middle-to-upper epidermis,as well as in the middle-to-lower epidermis,and locations of acantholysis may be associated with levels of anti-Dsg1 and anti-Dsg3 antibodies.

Progression of related diseases of desmoglein abnormal and pharmacological intervention / 中国药理学通报

Desmoglein,which is a kind of Ca2+ dependent desmosomal cadherins protein,is a major part of the desmosomes.The desmoglein that distributes in the epithelium,myocardium and other tissues plays a very important role in the cell junction.In recent years,the detection of the abnormal expression and function of the desmoglein was proved in many diseases,such as skin,mucous membrane and tumor related diseases.Drugs may have an important effect in the treatment of diseases by interfering with the expression and function of desmoglein.In this paper,the distribution of several subtypes of the family of desmosomes and their functions in the related diseases are reviewed,which may also provide some new clues for the new drug research on the target of desmogleins.

Desmoglein Compensation Theory: An explanations for Early Appearance of Oral lesions as Compared to Skin Lesions in Pemphigus Vulgaris

Pemphigus is a life-threatening autoimmune blistering disease targeting skin and mucous membranes. It is clinically characterized by flaccid blisters and erosions, while histologically shows intraepithelial acantholysis.  The disruption of desmoglein-dependent cell adhesion by autoantibodies is the basic pathophysiology in blister formation of pemphigus. The clinical and histological spectrum of pemphigus is complex and differs in various variants of pemphigus. This review offers an answer to why the splits associated with pemphigus foliaceus occur in the superficial layer of the epidermis, while those of pemphigus vulgaris occur deep in the epidermis. With the help of desmoglein compensation theory, it logically explains why oral erosions develop in patients with pemphigus vulgaris, but not in patients with pemphigus foliaceus and why some patients with pemphigus vulgaris have only oral involvement, but others have extensive lesions on both skin and mucous membranes. Learning objective: After completing this article, readers shall be familiar with the clinical presentations, histologic findings, immunopathology  of classical pemphigus and its  variants. It discusses the  desmoglein compensation theory of pathogenesis. along with the management of pemphigus.

Analysis on relationship between serum anti-desmoglein antibodies and disease in patients with pemphigus / 重庆医学

Objective To investigate the application value of ELISA for detecting the serum anti desmoglein (Dsg) 1 and Dsg 3 in the diagnosis and treatment of pemphigus .Methods Forty‐seven patients with pemphigus in our hospital from January to De‐cember 2014 were selected as the observation group and contemporaneous 52 patients with excluding pemphigus were selected as the control group .The Dsg antibodies were detected by using indirect immunofluorescence method and Dsg 1 and Dsg3 were deter‐mined by ELISA ;their correlation with pemphigus characteristics was analyzed .Results The sensitivity and specificity of ELISA for detecting anti‐Dsg antibodies were 95 .74% and 92 .31% respectively ,while which of IIF were 93 .62% and 86 .54% respective‐ly ,showing no statistically significant difference between the two test methods (P>0 .05) .In 30 cases of pemphigus vulgaris ,16 ca‐ses (16/30) were positive Dsg1 and Dsg 3 ,8 cases of pemphigus erythematosus and 5 cases pemphigus foliaceus were positive Dsg1 only ,and 2 cases of pemphigus vegetans were both positive Dsgl and Dsg3 .The Dsgl and Dsg3 titers of pemphigus vulgaris and pemphigus vegetans were 130 .85 ± 86 and 112 .30 ± 85 .05 ,respectively ,and the disease activity score was (5 .10 ± 1 .86) points ,the correlation coefficient(r)=0 .476(P=0 .008) ,r=0 .816(P=0 .001) ,respectively .The Dsgl titer of pemphigus erythematosus and pemphigus foliaceus were 142 .59 ± 78 .52 ,and the disease activity score was (2 .77 ± 0 .92) points(r=0 .800 ,P=0 .001) .Conclu‐sion ELISA for detecting Dsg1 and Dsg3 has high sensitivity and specificity ,and is conducive to the diagnosis of pemphigus and e‐valuation of disease severity .

Staphylococcal scalded skin syndrome – A case series with review of literature.

Staphylococcal scalded skin syndrome (SSSS) is an acute dermatological illness which requires prompt treatment. It is a condition associated with widespread exfoliation of skin caused by Staphylococcus aureus (SA). The toxins elaborated by these gram positive microorganisms especially the exfoliative toxins A and B causes the SSSS. Literature review mentions that only 5% of SA produces these exfoliative toxins. The main route of spread of the toxins is by the hematogenous spread and the process results in extensive damage to the epidermis. This case series reports the SSSS in two children and highlights the significance of promptly diagnosing this serious pediatric dermatological illness.

Mechanisms underlying the reversal of acantholysis in pemphigus by a cholinergic receptor agonist / 中华皮肤科杂志

Objective To evaluate the reversal effect of a cholinergic receptor agonist on acantholysis in pemphigus,and to investigate its mechanism.Methods Human HaCaT keratinocytes were co-cultured with pemphigus vulgaris immunoglobulin G (PV-IgG) to establish a cell model of pemphigus,then classified into two groups to be incubated with the cholinergic receptor agonist carbachol for 12 hours (test group) or remain untreated (control group).Cell dissociation assay was performed to quantitatively estimate the reversal effect of carbachol on acantholysis,and immunofluorescence assay to qualitatively assess the changes of desmosomal proteins.Radio-immunoprecipitation assay (RIPA) lysis buffer and Triton X-100 were used to lyse HaCaT cells to obtain total proteins and cytoplasmic proteins,and Western blot was conducted to determine the expression levels of adhesion-related proteins desmoglein 3 (Dsg3) and plakoglobin (PG) on the surface of HaCaT cells,as well as the phosphorylation levels of p38 mitogen activated protein kinase (p38 MAPK) and epidermal growth factor receptor (EGFR) at different time points.Quantitative polymerase chain reaction (qPCR) was performed to detect the mRNA expressions of the above surface proteins,and coimmunoprecipitation assay to qualitatively evaluate the interaction between Dsg3 and PG.Results The number of cell debris was significantly lower in the test group than in the control group (18.67 ± 2.52 vs.46.67 ± 2.03,t =11.22,P＜0.01).Immunofluorescence assay showed that carbachol could reverse the internalization of desmosomal molecules induced by PV-IgG.In the pemphigus cell model,the levels of total Dsg3 and PG as well as non-desmosomal Dsg3 were decreased,while the level of non-desmosomal PG increased,and the interaction between Dsg3 and PG was attenuated.When the pemphigus cell model was co-cultured with carbachol,these above changes were reversed.Carbachol also increased the mRNA levels (expressed as 2-△△Ct) of Dsg3 and PG from 1.428 ± 0.215 and 1.563 ± 0.247 in the control group to 4.974 ± 0.948 (t =3.65,P =0.01) and 13.420 ± 1.715 (t =6.85,P ＜ 0.01) in the test group respectively.In phosphorylation assay,carbachol inhibited the phosphorylation of EGFR,but had no significant effect on that of p38 MAPK.Conclusions The cholinergic receptor agonist carbachol can reverse acantholysis in pemphigus,likely by inhibiting the internalization of Dsg3 and PG,enhancing their expressions and interaction,and suppressing the phosphorylation of the key signaling molecule for acantholysis,EGFR.

The value of trichoscopy in the differential diagnosis of scalp lesions in pemphigus vulgaris and pemphigus foliaceus

BACKGROUND: Trichoscopy is becoming increasingly popular in diagnosing hair and scalp diseases. Scalp involvement in pemphigus is common. The scalp may be the first or only site of clinical manifestation of the disease. OBJECTIVE: The aim of this study was to analyze whether trichoscopy may be useful in aiding differential diagnosis of scalp lesions in patients with pemphigus vulgaris and pemphigus foliaceus. METHODS: Trichoscopy was performed in 19 patients with scalp lesions in the course of pemphigus (9 patients with pemphigus vulgaris and 10 with pemphigus foliaceus). In all patients, the diagnosis of scalp pemphigus was confirmed by histopathology. The working magnification was 20-fold and 70-fold. RESULTS: The most frequently observed trichoscopy features of pemphigus lesions were: extravasations (18/19; 94.7%) and yellow hemorrhagic crusts (11/19; 57.9%). Yellow dots with whitish halo were observed in 6/19 (31.6%) patients with pemphigus. White polygonal structures were observed in pemphigus foliaceus (6/10; 60%), but not in pemphigus vulgaris. Vascular abnormalities were more frequent in pemphigus vulgaris, when compared to pemphigus foliaceus, and were associated with a severe course of disease. Linear serpentine vessels were the most frequent vascular abnormality in patients with pemphigus vulgaris and pemphigus foliaceus (77.8% and 30%, respectively). CONCLUSION: Trichoscopy may serve as a useful supplementary method in the differential diagnosis of pemphigus, especially in cases of desquamative or exudative lesions limited to the scalp. Extravasations, yellow hemorrhagic crusts, yellow dots with whitish halo, white polygonal structures and linear serpentine vessels are trichoscopy features which may suggest the diagnosis of pemphigus. .

Pénfigo foliáceo variedad seborreica: reporte de un caso / Pemphigus foliaceus seborrheic variety: a case report / Pénfigo foliáceo variedade seborreica: relato de caso

El pénfigo eritematoso o seborréico, también denominado síndrome de Senear-Usher es la variedad leve y localizada del pénfigo foliáceo, de baja incidencia. La mayor parte de los casos se han reportado en adultos entre la segunda y tercera década de la vida, promedio de 54 años, sin predominio entre razas o sexo. Su etiología se debe a la presencia de anticuerpos anti IgG contra la desmogleina 1 de los queratinocitos de la capa granulosa. Clínicamente se presenta en forma de placas eritematoescamosas o eritematocostrosas bien definidas, de aspecto y distribución seborreica (cara, cuello y tronco), que se exacerban a la exposición solar. Su diagnóstico clínico puede ser difícil, ya que se superpone clínicamente con el lupus eritematoso discoide y la dermatitis seborreica, por lo cual es importante tenerlo en cuenta como diagnóstico diferencial en lesiones infiltradas en dorso nasal y región malar en patrón de alas de mariposa. Se presenta el caso clínico de un paciente con pénfigo foliáceo variedad seborreica una entidad de baja incidencia.

Pemphigus erythematosus or seborrheic, also called Senear - Usher syndrome,is a mild, localized variety of pemphigus foliaceus, an entity of low incidence. Most cases have been reported in adults between second and third decades of life, average 54 years, no difference between race or sex. Etiology is due to the presence of IgG antibodies against desmoglein 1 in keratinocytes of the granular layer. Clinically, defined erythematous plaques, seborrheic distribution aspect (face, neck and trunk), which are exacerbated by sun exposure. Clinical diagnosis can be difficult as clinically overlaps with discoid lupus erythematosus and seborrheic dermatitis. So, it is important to be considered as differential diagnosis in infiltrated nasal lesions, dorsum and malar region butterfly pattern. We report a case of pemphigus foliaceus- seborrheic variety, a low incidence entity.

O pênfigo eritematoso do tipo seborréico, também chamada de síndrome Senear -Usher é variedade leve e localizada do pênfigo foliáceo , de baixa incidência , a maioria dos casos foram relatados em adultos entre a segunda e terceira década de vida , com idade media de 54 anos, sem predominância entre raças ou sexo. A sua etiologia é devido à presença de anticorpos anti - IgG de desmogleína 1 dos queratinócitos da camada granular . Clinicamente, apresenta-se como placas eritematosas ou eritematocostrosas bem definidos, de aspecto e distribuição seborreica (face, pescoço e tronco), que são agravadas pela exposição ao sol. Seu diagnóstico clínico pode ser difícil, pois se sobrepõe clinicamente com lúpus eritematoso discóide e dermatite seborreica, por isso é importante te-lo em mente como diagnóstico diferencial nas lesões infiltradas no dorso da nariz e região malar com asas de borboleta. Apresenta-se o caso de um paciente com pênfigo foliáceo do tipo seborreico uma entidade de baixa incidência com poucos casos relatados na literatura.

IgG/IgA pemphigus reactive with desmoglein 1 with additional undetermined reactivity with epidermal basement membrane zone.

IgG/IgA pemphigus is an extremely rare subset of pemphigus, showing anti-keratinocyte cell surface antibodies of both IgG and IgA classes. Herein, we describe a unique case of IgG/IgA pemphigus with clinical features of edematous erythema and peripheral vesiculopustules. Histopathology showed the presence of subcorneal pustules and acantholytic blisters in the mid-epidermis with neutrophilic infiltration and eosinophilic spongiosis. Direct immunofluorescence of perilesional skin showed both IgG and IgA deposits to keratinocyte cell surfaces and unusual granular deposits of IgG, IgM, and C3 along basement membrane zone. On enzyme linked immunosorbent assay , the auto-antibodies were found to be reactive to desmoglein 1 antigen. Various clinical, histopathological, and immunological findings in our case overlapped with the features of IgA pemphigus, pemphigus herpetiformis, and pemphigus foliaceus. These findings indicate that IgG/IgA pemphigus may be a transitional form between IgA pemphigus and pemphigus herpetiformis, and thus provides insight into the pathogenicity of this rare disorder.